tbuckley/cabot-search huggingface dataset:
Aberrant T-cell exhaustion in severe combined immunodeficiency survivors with poor T-cell reconstitution after transplantation
Authors: Roxane Labrosse, Ines Boufaied, Benoîte Bourdin, Saideep Gona, Haley E. Randolph, Brent R. Logan, Sara Bourbonnais, Chloé Berthe, Wendy Chan, Rebecca H. Buckley, Roberta E. Parrott, Geoffrey D.E. Cuvelier, Neena Kapoor, Sharat Chandra, Blachy J. Dávila Saldaña, Hesham Eissa, Fred D. Goldman, Jennifer Heimall, Richard O’Reilly, Sonali Chaudhury, Edward A. Kolb, Shalini Shenoy, Linda M. Griffith, Michael Pulsipher, Donald B. Kohn, Luigi D. Notarangelo, Sung-Yun Pai, Morton J. Cowan, Christopher C. Dvorak, Élie Haddad, Jennifer M. Puck, Luis B. Barreiro, Hélène Decaluwe
Journal: Journal of Allergy and Clinical Immunology (2022)

Severe combined immunodeficiency (SCID) comprises rare inherited disorders of immunity that require definitive treatment through hematopoietic cell transplantation (HCT) or gene therapy for survival. Despite successes of allogeneic HCT, many SCID patients experience incomplete immune reconstitution, persistent T-cell lymphopenia, and poor long-term outcomes.
Prospective cohort study of psoriatic arthritis risk in patients with psoriasis in a real-world psoriasis registry
Authors: Alexis Ogdie, Ryan W. Harrison, Robert R. McLean, Tin-chi Lin, Mark Lebwohl, Bruce E. Strober, Joe Zhuo, Vardhaman Patel, Philip J. Mease
Journal: Journal of the American Academy of Dermatology (2022)

BackgroundThe characteristics that predict the onset of psoriatic arthritis (PsA) among patients with psoriasis (PsO) may inform diagnosis and treatment.ObjectiveTo develop a model to predict the 2-year risk of developing PsA among patients with PsO.MethodsThis was a prospective cohort study of patients in the CorEvitas Psoriasis Registry without PsA at enrollment and with 24-month follow-up. Unregularized and regularized logistic regression models were developed and tested using descriptive variables to predict dermatologist-identified PsA at 24 months. Model performance was compared using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity.ResultsA total of 1489 patients were included. Nine unique predictive models were developed and tested. The optimal model, including Psoriasis Epidemiology Screening Tool (PEST), body mass index (BMI), modified Rheumatic Disease Comorbidity Index, work status, alcohol use, and patient-reported fatigue, predicted the onset of PsA within 24 months (AUC = 68.9%, sensitivity = 82.9%, specificity = 48.8%). A parsimonious model including PEST and BMI had similar performance (AUC = 68.8%; sensitivity = 92.7%, specificity = 36.5%).LimitationsPsA misclassification bias by dermatologists.ConclusionPEST and BMI were important factors in predicting the development of PsA in patients with PsO over 2 years and thereby foundational for future PsA risk model development. The characteristics that predict the onset of psoriatic arthritis (PsA) among patients with psoriasis (PsO) may inform diagnosis and treatment. To develop a model to predict the 2-year risk of developing PsA among patients with PsO. This was a prospective cohort study of patients in the CorEvitas Psoriasis Registry without PsA at enrollment and with 24-month follow-up. Unregularized and regularized logistic regression models were developed and tested using descriptive variables to predict dermatologist-identified PsA at 24 months. Model performance was compared using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. A total of 1489 patients were included. Nine unique predictive models were developed and tested. The optimal model, including Psoriasis Epidemiology Screening Tool (PEST), body mass index (BMI), modified Rheumatic Disease Comorbidity Index, work status, alcohol use, and patient-reported fatigue, predicted the onset of PsA within 24 months (AUC = 68.9%, sensitivity = 82.9%, specificity = 48.8%). A parsimonious model including PEST and BMI had similar performance (AUC = 68.8%; sensitivity = 92.7%, specificity = 36.5%). PsA misclassification bias by dermatologists. PEST and BMI were important factors in predicting the development of PsA in patients with PsO over 2 years and thereby foundational for future PsA risk model development.
Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19
Authors: Carolyn T. Bramante, Jared D. Huling, Christopher J. Tignanelli, John B. Buse, David M. Liebovitz, Jacinda M. Nicklas, Kenneth Cohen, Michael A. Puskarich, Hrishikesh K. Belani, Jennifer L. Proper, Lianne K. Siegel, Nichole R. Klatt, David J. Odde, Darlette G. Luke, Blake Anderson, Amy B. Karger, Nicholas E. Ingraham, Katrina M. Hartman, Via Rao, Aubrey A. Hagen, Barkha Patel, Sarah L. Fenno, Nandini Avula, Neha V. Reddy, Spencer M. Erickson, Sarah Lindberg, Regina Fricton, Samuel Lee, Adnin Zaman, Hanna G. Saveraid, Walker J. Tordsen, Matthew F. Pullen, Michelle Biros, Nancy E. Sherwood, Jennifer L. Thompson, David R. Boulware, Thomas A. Murray
Journal: New England Journal of Medicine (2022)

Early treatment to prevent severe coronavirus disease 2019 (Covid-19) is an important component of the comprehensive response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic.
Drawing the Line on Glycemia in Pregnancy
Authors: Michael F. Greene
Journal: New England Journal of Medicine (2022)

In the first decade of this millennium, convincing data showing that screening for and treatment of gestational diabetes mellitus improve both maternal and fetal outcomes1,2 ended debates within the obstetrical community about the usefulness of screening for gestational diabetes. Essentially all U.S. professional societies now recommend universal biochemical screening with an oral glucose-tolerance test (OGTT) at 24 to 28 weeks' gestation.3 Accordingly, current research aims to improve the benefits of screening for gestational diabetes and to minimize potential harms. Although some sources have recommended glucose-tolerance testing in early pregnancy for women at high risk for diabetes,4 a recent randomized trial . . .
Case 25-2022: A 25-Year-Old Woman with Headache and Blurred Vision
Authors: Christina M. Marra, Saurabh Rohatgi, Allyson K. Bloom, Kristopher T. Kahle, Amelia K. Haj
Journal: New England Journal of Medicine (2022)

A 25-year-old woman was evaluated for worsening headaches, photophobia, nausea, vomiting, and blurred vision. MRI revealed hydrocephalus and leptomeningeal enhancement. CSF analysis revealed neutrophilic pleocytosis.
Rapid Nanopore Sequencing–Based Screen for Aneuploidy in Reproductive Care
Authors: Shan Wei, Alexandre Djandji, Miriam T Lattin, Odelia Nahum, Nataly Hoffman, Claudia Cujar, Refik Kayali, Cengiz Cinnioglu, Ronald Wapner, Mary D'Alton, Brynn Levy, Zev Williams
Journal: New England Journal of Medicine (2022)
Treatment for Mild Chronic Hypertension during Pregnancy
Authors: Alan T Tita, Jeff M Szychowski, William W Andrews
Journal: New England Journal of Medicine (2022)

The benefits and safety of the treatment of mild chronic hypertension (blood pressure, <160/100 mm Hg) during pregnancy are uncertain.Data are needed on whether a strategy of targeting a blood pressure of less than 140/90 mm Hg reduces the incidence of adverse pregnancy outcomes without compromising fetal growth. METHODSIn this open-label, multicenter, randomized trial, we assigned pregnant women with mild chronic hypertension and singleton fetuses at a gestational age of less than 23 weeks to receive antihypertensive medications recommended for use in pregnancy (active-treatment group) or to receive no such treatment unless severe hypertension (systolic pressure, ≥160 mm Hg; or diastolic pressure, ≥105 mm Hg) developed (control group).The primary outcome was a composite of preeclampsia with severe features, medically indicated preterm birth at less than 35 weeks' gestation, placental abruption, or fetal or neonatal death.The safety outcome was small-forgestational-age birth weight below the 10th percentile for gestational age.Secondary outcomes included composites of serious neonatal or maternal complications, preeclampsia, and preterm birth. RESULTSA total of 2408 women were enrolled in the trial.The incidence of a primary-outcome event was lower in the active-treatment group than in the control group (30.2% vs. 37.0%), for an adjusted risk ratio of 0.82 (95% confidence interval [CI], 0.74 to 0.92; P<0.001).The percentage of small-for-gestational-age birth weights below the 10th percentile was 11.2% in the active-treatment group and 10.4% in the control group (adjusted risk ratio, 1.04; 95% CI, 0.82 to 1.31; P = 0.76).The incidence of serious maternal complications was 2.1% and 2.8%, respectively (risk ratio, 0.75; 95% CI, 0.45 to 1.26), and the incidence of severe neonatal complications was 2.0% and 2.6% (risk ratio, 0.77; 95% CI, 0.45 to 1.30).The incidence of any preeclampsia in the two groups was 24.4% and 31.1%,respectively (risk ratio, 0.79; 95% CI, 0.69 to 0.89), and the incidence of preterm birth was 27.5% and 31.4% (risk ratio, 0.87; 95% CI, 0.77 to 0.99). CONCLUSIONSIn pregnant women with mild chronic hypertension, a strategy of targeting a blood pressure of less than 140/90 mm Hg was associated with better pregnancy outcomes than a strategy of reserving treatment only for severe hypertension, with no increase in the risk of small-for-gestational-age birth weight.
Monkeypox: a new differential diagnosis when addressing genital ulcer disease
Authors: Joseph Griffiths-Acha, Miguel Vela-Ganuza, Claudia Sarró-Fuente, José Luis López-Estebaranz
Journal: British Journal of Dermatology (2022)

We describe a case of genital ulcer and inguinal adenopathies that were attributable to monkeypox virus infection. We suggest clinicians adopt a low threshold for suspicion, particularly when evaluating genital ulcer disease.
<i>FGF2</i> Signaling Is Required for the Development of Neuronal Circuits Regulating Blood Pressure
Authors: Rosanna Dono, Jörg Faulhaber, Antonella Galli, Aimée Zuniga, Tilmann Volk, Gemma Texido, Rolf Zeller, Heimo Ehmke
Journal: Circulation Research (2002)

Fibroblast growth factor 2 (FGF2) signaling is involved in angiogenesis, vascular contractility, and cardiac hypertrophy. Mice lacking a functional FGF2 gene (FGF2 −/− ) are hypotensive, but the primary physiological role of FGF2 in cardiovascular homeostasis remained unknown. Using a chicken FGF2 ( cFGF2 ) transgene under control of the Wnt-1 promotor, we selectively re-expressed FGF2 in the developing nervous system of FGF2 −/− (transgenic FGF2 mutant) embryos. Expression of the cFGF2 transgene in the developing nervous system, including its autonomic region, was limited to the period between embryonic day 9.5 and 14.5. Significantly, no FGF2 re-expression was detected in developing heart and blood vessels. Pharmacological analysis revealed a normalization of the blood pressure response to isoproterenol-induced vasodilation in adult transgenic FGF2 mutant mice. In addition, the hypotensive phenotype was rescued in 1 line (of 2) transgenic FGF2 mutant adult mice having expressed higher levels of cFGF2 proteins during nervous system development. These genetic studies indicate that FGF2 signaling is essential for complete development of the neural circuitry required for central regulation of blood pressure, whereas it appears dispensable for blood pressure control in the healthy adult. The full text of this article is available at http://www.circresaha.org.
A low-power stretchable neuromorphic nerve with proprioceptive feedback
Authors: Yeongjun Lee, Yuxin Liu, Dae-Gyo Seo, Jin Young Oh, Yeongin Kim, Jinxing Li, Jiheong Kang, Jaemin Kim, Jaewan Mun, Amir M. Foudeh, Zhenan Bao, Tae-Woo Lee
Journal: Nature Biomedical Engineering (2022)
In situ hydrogel capturing nitric oxide microbubbles accelerates the healing of diabetic foot
Authors: Yingzheng Zhao, Lanzi Luo, Lantian Huang, Yingying Zhang, Mengqi Tong, Hanxiao Pan, Jianxun Shangguan, Qing Yao, Shihao Xu, Helin Xu
Journal: Journal of Controlled Release (2022)
Prevalence of Leukopenia and Associated Outcomes in Patients With Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis
Authors: Leo L. Wang, Megan H. Noe, Robert G. Micheletti
Journal: JAMA Dermatology (2022)

This case series compares the factors, comorbidities, and complications associated with leukopenia between patients with and without leukopenia on hospital admission.
A non‐metabolic function of hexokinase 2 in small cell lung cancer: promotes cancer cell stemness by increasing USP11‐mediated CD133 stability
Authors: Juhong Wang, Fei Shao, Yannan Yang, Wei Wang, Xueying Yang, Renda Li, Hong Cheng, Sijin Sun, Xiaoli Feng, Yibo Gao, Jie He, Zhimin Lu
Journal: Cancer Communications (2022)

Abstract Background Maintenance of cancer stem‐like cell (CSC) stemness supported by aberrantly regulated cancer cell metabolism is critical for CSC self‐renewal and tumor progression. As a key glycolytic enzyme, hexokinase 2 (HK2) plays an instrumental role in aerobic glycolysis and tumor progression. However, whether HK2 directly contribute to CSC stemness maintenance in small cell lung cancer (SCLC) is largely unclear. In this study, we aimed to investgate whether HK2 independent of its glycolytic activity is directly involved in stemness maintenance of CSC in SCLC. Methods Immunoblotting analyses were conducted to determine the expression of HK2 in SCLC CSCs and their differentiated counterparts. CSC‐like properties and tumorigenesis of SCLC cells with or without HK2 depletion or overexpression were examined by sphere formation assay and xenograft mouse model. Immunoprecipitation and mass spectrometry analyses were performed to identify the binding proteins of CD133. The expression levels of CD133‐associated and CSC‐relevant proteins were evaluated by immunoblotting, immunoprecipitation, immunofluorescence, and immunohistochemistry assay. RNA expression levels of Nanog , POU5F1 , Lin28 , HK2 , Prominin‐1 were analyzed through quantitative reverse transcription PCR. Polyubiquitination of CD133 was examined by in vitro or in vivo ubiquitination assay. CD133 + cells were sorted by flow cytometry using an anti‐CD133 antibody. Results We demonstrated that HK2 expression was much higher in CSCs of SCLC than in their differentiated counterparts. HK2 depletion inhibited CSC stemness and promoted CSC differentiation. Mechanistically, non‐mitochondrial HK2 directly interacted with CD133 and enhanced CD133 expression without affecting CD133 mRNA levels. The interaction of HK2 and CD133 promoted the binding of the deubiquitinase ubiquitin‐specific protease 11 (USP11) to CD133, thereby inhibiting CD133 polyubiquitylation and degradation. HK2‐mediated upregulation of CD133 expression enhanced the expression of cell renewal regulators, SCLC cell stemness, and tumor growth in mice. In addition, HK2 expression was positively correlated with CD133 expression in human SCLC specimens, and their expression levels were associated with poor prognosis of SCLC patients. Conclusions These results revealed a critical non‐metabolic function of HK2 in promotion of cancer cell stemness. Our findings provided new insights into the multifaceted roles of HK2 in tumor development.
Secretin alleviates biliary and liver injury during late-stage primary biliary cholangitis via restoration of secretory processes
Authors: Lindsey Kennedy, Guido Carpino, Travis Owen, Ludovica Ceci, Debjyoti Kundu, Vik Meadows, Konstantina Kyritsi, Antonio Franchitto, Paolo Onori, Abdulkadir Isidan, Wenjun Zhang, Burcin Ekser, Domenico Alvaro, Eugenio Gaudio, M. Eric Gershwin, Heather Francis, Shannon Glaser, Gianfranco Alpini
Journal: Journal of Hepatology (2022)
Nestin as a diagnostic and prognostic marker for combined hepatocellular-cholangiocarcinoma
Authors: Julien Calderaro, Luca Di Tommaso, Pascale Maillé, Aurélie Beaufrère, Cong Trung Nguyen, Lara Heij, Viviane Gnemmi, Rondell P. Graham, Frédéric Charlotte, Suzanne Chartier, Dominique Wendum, Mukul Vij, Daniela Allende, Alba Diaz, Carla Fuster, Benjamin Rivière, Astrid Herrero, Jérémy Augustin, Katja Evert, Diego Francesco Calvisi, Wei Qiang Leow, Howard Ho Wai Leung, Jan Bednarsch, Emmanuel Boleslawski, Mohamed Rela, Anthony Wing-Hung Chan, Alejandro Forner, Maria Reig, Anaïs Pujals, Loetitia Favre, Manon Allaire, Olivier Scatton, Arnaud Uguen, Eric Trépo, Lukas Otero Sanchez, Denis Chatelain, Myriam Remmelink, Camille Boulagnon-Rombi, Céline Bazille, Nathalie Sturm, Benjamin Menahem, Eric Frouin, David Tougeron, Christophe Tournigand, Emmanuelle Kempf, Haeryoung Kim, Massih Ningarhari, Sophie Michalak-Provost, Jakob Nikolas Kather, Annette S.H. Gouw, Purva Gopal, Raffaele Brustia, Eric Vibert, Kornelius Schulze, Darius F. Rüther, Sören A. Weidemann, Rami Rhaiem, Jean-Charles Nault, Alexis Laurent, Giuliana Amaddeo, Hélène Regnault, Eleonora de Martin, Christine Sempoux, Pooja Navale, Jayendra Shinde, Ketan Bacchuwar, Maria Westerhoff, Regina Cheuk-Lam Lo, Mylène Sebbagh, Catherine Guettier, Marie Lequoy, Mina Komuta, Marianne Ziol, Valérie Paradis, Jeanne Shen, Stefano Caruso
Journal: Journal of Hepatology (2022)
Response to “Response to Fulk et al’s ‘Geographic practice preferences of graduating medical students pursuing careers in dermatology’”
Authors: Katelyn J. Rypka, Travis S. Fulk, Laurel L. Wessman, Rachit Gupta, Robert T. Brodell, Ronda S. Farah, Cindy Firkins Smith, Kevin J. Gaddis, Matthew Mansh
Journal: Journal of the American Academy of Dermatology (2022)
Chronic Obstructive Pulmonary Disease
Authors: Peter J. Barnes
Journal: New England Journal of Medicine (2000)

Chronic obstructive pulmonary disease (COPD) is characterized by the progressive development of airflow limitation that is not fully reversible.1 The term COPD encompasses chronic obstructive bronchitis, with obstruction of small airways, and emphysema, with enlargement of air spaces and destruction of lung parenchyma, loss of lung elasticity, and closure of small airways. Chronic bronchitis, by contrast, is defined by the presence of a productive cough of more than three months' duration for more than two successive years. The cough is due to hypersecretion of mucus and is not necessarily accompanied by airflow limitation. However, there is some epidemiologic evidence that . . .
Adrenocortical Carcinoma
Authors: Tobias Else, Alex C. Kim, Aaron Sabolch, Victoria M. Raymond, Asha Kandathil, Elaine M. Caoili, Shruti Jolly, Barbra S. Miller, Thomas J. Giordano, Gary D. Hammer
Journal: Endocrine Reviews (2013)

Abstract Adrenocortical carcinoma (ACC) is a rare endocrine malignancy, often with an unfavorable prognosis. Here we summarize the knowledge about diagnosis, epidemiology, pathophysiology, and therapy of ACC. Over recent years, multidisciplinary clinics have formed and the first international treatment trials have been conducted. This review focuses on evidence gained from recent basic science and clinical research and provides perspectives from the experience of a large multidisciplinary clinic dedicated to the care of patients with ACC.
Translational significance of CDKN2A/B homozygous deletion in isocitrate dehydrogenase-mutant astrocytoma
Authors: Shannon P Fortin Ensign, Robert B Jenkins, Caterina Giannini, Jann N Sarkaria, Evanthia Galanis, Sani H Kizilbash
Journal: Neuro-Oncology (2022)

Abstract Isocitrate dehydrogenase (IDH) 1 or 2 mutations confer a favorable prognosis compared to IDH-wildtype in astrocytoma, frequently denoting a lower grade malignancy. However, recent molecular profiling has identified specific aggressive tumor subgroups with clear clinical prognostic implications that are independent of histologic grading. The homozygous deletion of CDKN2A/B is the strongest implicated independent indicator of the poor prognosis within IDH-mutant astrocytoma, and the identification of this alteration in these lower histologic grade tumors transforms their biology toward an aggressive grade 4 phenotype clinically. CDKN2A/B homozygous deletion is now sufficient to define a grade 4 tumor in IDH-mutant astrocytomas regardless of histologic appearance, yet there are currently no effective molecularly informed targeted therapies for these tumors. The biological impact of CDKN2A/B homozygous deletion in IDH-mutant tumors and the optimal treatment strategy for this molecular subgroup remains insufficiently explored. Here we review the current understanding of the translational significance of homozygous deletion of CDKN2A/B gene expression in IDH-mutant astrocytoma and associated diagnostic and therapeutic implications.
Carnosol Inhibits <b>β</b>-Catenin Tyrosine Phosphorylation and Prevents Adenoma Formation in the C57BL/6J/Min/+ (Min/+) Mouse
Authors: Amy E. Moran, Adelaide M. Carothers, Michael J. Weyant, Mark Redston, Monica M. Bertagnolli
Journal: Cancer Research (2005)

Abstract Carnosol, a constituent of the herb, rosemary, has shown beneficial medicinal and antitumor effects. Using the C57BL/6J/Min/+ (Min/+) mouse, a model of colonic tumorigenesis, we found that dietary administration of 0.1% carnosol decreased intestinal tumor multiplicity by 46%. Previous studies showed that tumor formation in the Min/+ mouse was associated with alterations in the adherens junctions, including an increased expression of tyrosine-phosphorylated β-catenin, dissociation of β-catenin from E-cadherin, and strongly reduced amounts of E-cadherin located at lateral plasma membranes of histologically normal enterocytes. Here, we confirm these findings and show that treatment of Min/+ intestinal tissue with carnosol restored both E-cadherin and β-catenin to these enterocyte membranes, yielding a phenotype similar to that of the Apc+/+ wild-type (WT) littermate. Moreover, treatment of WT intestine with the phosphatase inhibitor, pervanadate, removed E-cadherin and β-catenin from the lateral membranes of enterocytes, mimicking the appearance of the Min/+ tissue. Pretreatment of WT tissue with carnosol inhibited the pervanadate-inducible expression of tyrosine-phosphorylated β-catenin. Thus, the ApcMin allele produces adhesion defects that involve up-regulated expression of tyrosine-phosphorylated proteins, including β-catenin. Moreover, these data suggest that carnosol prevents Apc-associated intestinal tumorigenesis, potentially via its ability to enhance E-cadherin-mediated adhesion and suppress β-catenin tyrosine phosphorylation.
Evidence of SARS-CoV-2 spike protein on retrieved thrombi from COVID-19 patients
Authors: Manuela De Michele, Giulia d’Amati, Martina Leopizzi, Marta Iacobucci, Irene Berto, Svetlana Lorenzano, Laura Mazzuti, Ombretta Turriziani, Oscar G. Schiavo, Danilo Toni
Journal: Journal of Hematology & Oncology (2022)

The pathophysiology of COVID-19-associated coagulopathy is complex and not fully understood. SARS-CoV-2 spike protein (SP) may activate platelets and interact with fibrin(ogen). We aimed to investigate whether isolated SP can be present in clots retrieved in COVID-19 patients with acute ischemic stroke (by mechanical thrombectomy) and myocardial infarction. In this pilot study, we could detect SP, but not nucleocapsid protein, on platelets of COVID-19 patients' thrombi. In addition, in all three COVID-19 thrombi analyzed for molecular biology, no SARS-CoV-2 RNA could be detected by real-time polymerase chain reaction. These data could support the hypothesis that free SP, besides the whole virus, may be the trigger of platelet activation and clot formation in COVID-19.